Analysis of candidate gene deficient mice cause insulin resistance in Spontaneously Hypertensive Rats

• Project/Area Number: 20591049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: IIZUKA Yoko The University of Tokyo, 医学部附属病院, 助教 (40420244)
• Co-Investigator(Kenkyū-buntansha): YAHAGI Naoya 筑波大学, 大学院・人間総合科学研究科, 准教授 (60420246)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: エネルギー / 糖質代謝異常 / 高血圧自然発症ラット(SHR) / 原因候補遺伝子 / kynurenine aminotransferase 1(KAT-1) / 高血圧 / インスリン抵抗性 / 交感神経活動亢進 / ノックアウトマウス / 肥満 / 高血圧自然発症ラット / kynurenine aminotransferase 1 / 交感神経亢進 / 欠損マウス / RNAiアデノウイルスベクター / 高血圧自然発症ラットSHR / ynurenine aminotransferase 1 / RNAiアデノウイルス

Research Abstract

1) Normal delivery, normal growth, and null expression of mRNA and protein in each organization of KAT-1 knockout mouse have been confirmed. KAT-1 knockout mouse demonstrates 2) significant increase of blood pressure under the normal chow, more increase of blood pressure under 12 weeks high salt diet by tail-cuff and telemetry system, 3) the rise of 24-hour urine catecholamine secretion under high salt diet, 4) significant increase of fast blood glucose, the rise of insulin resistance by insulin tolerance test under normal chow, 5) the decrease of the fat pat weight under high fat diet accompanied with increase in activity level.

Research Products

• [Journal Article] Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit. (2010)
  • Author(s): Takeuchi Y, Yahagi N, Iizuka Y, et al
  • Journal Title: J Biol Chem 285 Pages: 11681-91
  • Peer Reviewed
• [Journal Article] Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep(ob)(/)(ob) mice. (2009)
  • Author(s): Sekiya M, Yahagi N, Iizuka Y, et al
  • Journal Title: Biochem Biophys Res Commun 387 Pages: 511-5
  • Peer Reviewed
• [Journal Article] Ablation of neutral cholesterol ester hydrolase 1 accelerates atherosclerosis. (2009)
  • Author(s): Sekiya M, Yahagi N, et al
  • Journal Title: Cell Metab 10 Pages: 219-28
  • Peer Reviewed
• [Journal Article] Hormone-sensitive lipase is involved in hepatic cholesterol ester hydrolysis. (2008)
  • Author(s): Sekiya M, Yahagi N, Iizuka Y, et al
  • Journal Title: J Lipid Res 49 Pages: 1829-38
  • Peer Reviewed
• [Journal Article] Overexpression of nuclear SREBP-2 in pancreatic beta -cells results in cholesterol accumulation leading to insulin secretion defects and diabetes: A new model for beta-cell lipotoxicity. (2008)
  • Author(s): Ishikawa M, Yahagi N, et al
  • Journal Title: J Lipid Res 49 Pages: 2524-34
  • Peer Reviewed
• [Journal Article] Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages. (2008)
  • Author(s): Okazaki H, Yahagi N, et al
  • Journal Title: J Biol Chem 283 Pages: 33357-64
  • Peer Reviewed
• [Journal Article] Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets. (2008)
  • Author(s): Kato T, Yahagi N, et al
  • Journal Title: Diabetes 57 Pages: 2382-92
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity and insulin resistance. (2008)
  • Author(s): Inoue N, Yahagi N, et al
  • Journal Title: J Biol Chem 283 Pages: 21220-9
  • Peer Reviewed
• [Journal Article] Mouse Elovl-6 promoter is an SREBP target. (2008)
  • Author(s): Kumadaki S, Yahagi N, et al
  • Journal Title: Biochem Biophys Res Commun 368 Pages: 261-6
  • Peer Reviewed
• [Presentation] Establishment of kynurenine aminotransferase 1 ( KAT-1) knockout mice as an animal model of spontaneous hypertension and insulin resistance observedin the spontaneously hypertensive rats (2010)
  • Author(s): 飯塚陽子, 矢作直也, et al
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-15
• [Presentation] SHRの高血圧とインスリン抵抗性原因遺伝子kynurenine aminotransferase 1(KAT-1)欠損マウスの作製と解析 (2010)
  • Author(s): 飯塚陽子, 他
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-15
• [Presentation] SHRの高血圧とインスリン抵抗性原因遺伝子kynurenine aminotransferase 1(KAT-1)欠損マウスの作製と解析 (2010)
  • Author(s): 飯塚陽子、矢作直也、他
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-29
• [Presentation] SHRの高血圧とインスリン抵抗性原因遺伝子kynurenine aminotransferase 1 (KAT-1)欠損マウスの作製と解析 (2010)
  • Author(s): 飯塚陽子, 他
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-29
• [Presentation] kynurenine aminotransferase 1(KAT-1)のRNAiノックダウンによる解析 (2009)
  • Author(s): 飯塚陽子、矢作直也、他
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-23
• [Presentation] kynurenine aminotransferase-1(KAT-1)のRNAiノックダウンによる解析 (2009)
  • Author(s): 飯塚陽子, 大須賀淳一, 和泉梢, 周宇璢, 代田翠, 喬荊, 李勇学, 関谷元博, 五十嵐正樹, 武内謙憲, 高瀬暁, 高梨幹生, 西真貴子, 久保田みどり, 熊谷真義, 太田啓介, 泉田欣彦, 矢作直也, 大橋健, 島野仁, 石橋俊, 藤田敏郎, 山田信博, 後藤田貴也, 門脇孝
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] A search for genes underlying visceral fat accumulation in spontaneously hypertensive rat (SHR) (2008)
  • Author(s): 飯塚陽子, 矢作直也, et al
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 筑波
  • Year and Date: 2008-07-11
• [Presentation] 高血圧自然発症ラット(SHR)における内臓脂肪蓄積関連遺伝子の同定 (2008)
  • Author(s): 飯塚陽子、矢作直也、他
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-22